Ten percent of patients with renal cell carcinoma will develop brain metastases. Patients frequently develop brain metastasis even while their extracranial disease remains under control. Unfortunately, treatment options are limited, and most current clinical trials in the US exclude patients with brain metastases. Our limited understanding of the molecular drivers of brain metastases has hampered the development of novel therapeutics for this common complication of cancer. Our group recently completed whole-exome sequencing of 104 brain metastases, primary tumors and normal tissue across many histologies. In this initial dataset, which included only eight brain metastases from renal cell carcinoma, we detected clinically actionable alterations that were unique to the brain metastases. We have now assembled a large cohort of renal cell carcinoma brain metastases. Our proposed genomic analysis will focus on characterizing the molecular alterations in brain metastases from RCC. We will analyze brain metastases, extracranial metastases, cerebrospinal fluid, and plasma samples before and after targeted therapy or immune checkpoint blockade therapy to identify genetic alterations driving their clinical behavior, including resistance to therapy. Identification of these mutations will aid in the design of more effective targeted treatments to treat brain metastases.

Public Health Relevance

In this study, we propose to identify potential drivers and therapeutic targets of newly diagnosed and recurrent brain metastases from renal cell cancer. Our application is relevant to the public health because there are no effective systemic therapies for patients with brain metastases from renal cell carcinoma. Relevant to the NIH mission, the overarching objective of this study is to identify genetic changes that are associated with more aggressive phenotypes of renal cell carcinoma, with the goal to identify optimal therapeutic approaches for this common neoplasm.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA220253-02
Application #
9773001
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Mckee, Tawnya C
Project Start
2018-09-01
Project End
2020-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114